Autologous mesenchymal stem cell treatment increased T regulatory cells with no effect on disease activity in two systemic erythematosus patients

Facultad de Medicina, Universidad de los Andes, Santiago, Chile.
Lupus (Impact Factor: 2.48). 11/2009; 19(3):317-22. DOI: 10.1177/0961203309348983
Source: PubMed

ABSTRACT Mesenchymal stem cells (MSCs) exert suppressive effects in several disease models including lupus prone mice. However, autologous MSC therapy has not been tested in human systemic lupus erythematosus (SLE). We evaluate the safety and efficacy of bone marrow (BM)-derived MSCs in two SLE patients; the suppressor effect of these cells in-vitro and the change in CD4+CD25+FoxP3+ T regulatory (Treg) cells in response to treatment. Two females (JQ and SA) of 19 and 25 years of age, fulfilling the 1997 American College of Rheumatology (ACR) criteria for SLE were infused with autologous BM-derived MSCs. Disease activity indexes and immunological parameters were assessed at baseline, 1, 2, 7 and 14 weeks. Peripheral blood lymphocyte (PBL) subsets and Treg cells were quantitated by flow cytometry, and MSCs tested for in-vitro suppression of activation and proliferation of normal PBLs. No adverse effects or change in disease activity indexes were noted during 14 weeks of follow-up, although circulating Treg cells increased markedly. Patient MSCs effectively suppressed in-vitro PBL function. However, JQ developed overt renal disease 4 months after infusion. MSC infusion was without adverse effects, but did not modify initial disease activity in spite of increasing CD4+CD25+FoxP3+ cell counts. One patient subsequently had a renal flare. We speculate that the suppressive effects of MSC-induced Treg cells might be dependent on a more inflammatory milieu, becoming clinically evident in patients with higher degrees of disease activity.

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    • "Today, it is well accepted that MSCs have important immunosuppressive properties over the entire immune system , mainly exerting their effects on T, B, NK, and dendritic cells [8] [9]. This immunomodulatory capacity of MSCs has opened new therapeutic prospects in the management of proinflammatory and autoimmune pathologies [10] [11] [12]. The therapeutic potential of MSCs has been demonstrated in a variety of autoimmune disease models including graftversus-host disease (GVDH) [13], experimental autoimmune encephalomyelitis (EAE) [14] [15], collagen-induced arthritis "
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    • "Although MSCs from the SLE patients show immunosuppressive activity, they undergo senescence relatively faster than MSC from age matched healthy controls [40] [41]. Autologous MSC therapy in two SLE patients was safe but did not reduce the disease activity [42]. A direct link between the SLE and SNPs in genes of the inflammasomes has been demonstrated [43]. "
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